Ocular pharmacokinetics assessed by in‐vivo microdialysis
Gerhard Garhöfer
Abstract
Gerhard Garhöfer
Abstract
Summary A key challenge in drug development is to obtain reliable concentration‐time profiles in potential target tissues. For the eye, data regarding drug concentration in the anterior chamber and the vitreous is crucial for optimizing the dosing for topically applied therapies. Given that in most cases, invasive serial probe sampling in humans is not possible for ethical reasons, data regarding drug penetration in the eye routinely relies on in‐vivo animal models. Classical pharmacokinetic models are based on obtaining single samples of the anterior chamber and the vitreous at consecutive timepoints in different animals. In contrast to that, in‐vivo microdialysis offers a new possibility to determine statistically robust pharmacokinetic profiles without including large numbers of animals. As described previously described for other tissues, microdialysis allows for the continuous in‐vivo sampling of analytes in a tissue by implantation of a probe with a semi‐permeable membrane in the target tissue. The current talk aims to give an overview about the microdialysis technique with special regards to the ocular tissues. In addition, advantages and potential disadvantages as well as the limitations of the technique will be discussed.
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Summary A key challenge in drug development is to obtain reliable concentration‐time profiles in potential target tissues. For the eye, data regarding drug concentration in the anterior chamber and the vitreous is crucial for optimizing the dosing for topically applied therapies. Given that in most cases, invasive serial probe sampling in humans is not possible for ethical reasons, data regarding drug penetration in the eye routinely relies on in‐vivo animal models. Classical pharmacokinetic models are based on obtaining single samples of the anterior chamber and the vitreous at consecutive timepoints in different animals. In contrast to that, in‐vivo microdialysis offers a new possibility to determine statistically robust pharmacokinetic profiles without including large numbers of animals. As described previously described for other tissues, microdialysis allows for the continuous in‐vivo sampling of analytes in a tissue by implantation of a probe with a semi‐permeable membrane in the target tissue. The current talk aims to give an overview about the microdialysis technique with special regards to the ocular tissues. In addition, advantages and potential disadvantages as well as the limitations of the technique will be discussed.
Key concepts: Microdialysis, In vivo, Pharmacokinetics, Biomedical engineering, Sampling (signal processing), Medicine, Pharmacology, Pathology